[233] FGFR1 Amplification in Breast Cancers with Unfavorable Features

Katrin Pfaltz, Sandra Schneider, Serenella Eppenberger-Castori, Coya Tapia. University Bern, Bern, Switzerland; University Hospital Basel, Basel, Switzerland

Background: The fibroblast growth factor receptor 1 (FGFR1) gene, located at chromosome 8p12, encodes a tyrosine kinase. FGFR1 is involved in cell proliferation, survival, migration, and differentiation. FGFR1 can be targeted by a small molecule (FGFR inhibitor) leading to significant tumor shrinkage. FGFR1 amplified tumors seem to be targetable/responsive to FGFR inhibitors. Therefore, we validated FGFR1 gene status in a large cohort of breast cancers to evaluate FGFR inhibitors as a possible therapeutic option in this disease.
Design: We hybridized tissue mirco-arrays (TMA) with 907 breast cancers using a commercially available fluorescent in-situ hybridization probe (FGFR1/CEN8; ZytoVision®). Normal gene status was considered as a ratio (FGFR1/CEN8): 0.8-1.9, amplification was defined as ratio ≥2.0, polysomy was defined as >4 FGFR1 and CEN8 signals.
Results: FGFR1 amplification was observed in 8.9% (n=81), a normal gene status was found in 80.7% (n=732), and a polysomy was detected in 10.2% (n=93) of all tumors. FGFR1 amplified breast cancers showed the following features: 72.8% (59/81) ductal, 45.5% (35/77) high grade (G3), 16% (12/75) HER2 of 2+/3+, 55.5% (35/63) positive lymph nodes, and 18% (13/72) recurrence. Comparing T-categories (T1, T2, T3) FGFR1 amplified breast cancers and non-amplified tumors showed the following results: T1: 25% vs. 34%, T2: 56% vs. 48%, T3: 9% vs. 6%.
Conclusions: FGFR1 amplification is especially prevalent in breast cancers with unfavorable/aggressive features such as a high tumor grade (45.5%), large tumor diameter, and metastasis (55.5%). These patients are a clinically relevant group since they require aggressive adjuvant treatment. The detection of FGFR1 amplification could help in the identification of some patients already at higher risk which might benefit from a new therapeutic option with FGFR1 inhibitors.
Category: Breast

Wednesday, March 21, 2012 9:30 AM

Poster Session V # 59, Wednesday Morning

 

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